Melanomas are tumors of the skin, less frequently of mucous membranes, some of which are benign. Malignant melanomas are carcinomas of neuroectodermal origin generally derived from melanocytes (pigment-producing cells), sometimes from mucous membranes, the chorioid coat or the meninges. There are several types of malignant melanoma which differ in localization, way of spreading and production of metastases.
Conventional treatment of melanoma includes surgery, radio- or chemotherapy, and the application of biological response modifiers. However, these methods have proved to be insufficient to combat the illness, e.g. to prevent tumor recurrence, and are complicated by a large number of severe side effects. Therefore, it is desirable to develop therapeutic approaches which overcome these drawbacks and can replace or be used in combination with conventional treatment.
Since the immune system seems to be heavily involved in the pathogenesis of this disease, the most suitable treatment would be a method of active immunotherapy, for example based on the application of specific antiidiotypic antibodies. Of special interest for therapeutic application are antiidiotypic antibodies of the internal image type which mimic the initial antigen and can substitute for it.
For tumor therapy, suitable antiidiotypic antibodies are those which are raised against antibodies specific for tumor associated antigens. In melanoma, one of the associated antigens (MAA) identified so far is the high molecular weight-melanoma associated antigen (HMW-MAA) with a molecular weight of &gt;1,000,000. Murine antiidiotypic monoclonal antibodies raised against an antibody to HMW-MAA have been disclosed in European Patent Application No. 428 485.
However, a major limitation in the use of said murine-derived antiidiotypic monoclonal antibodies as diagnostic and therapeutic agents is their immunogenicity as foreign proteins, their rather long persistence in the circulation, and the formation of damaging immune complexes. On the other hand, the treatment with human monoclonal antibodies is also limited since human hybridoma cell lines are hard to prepare, generally unstable, and do not produce monoclonal antibodies of appropriate specificity in sufficient quantities and at reasonable costs.
Accordingly, there is a need for antiidiotypic antibodies the application of which inheres a reduced risk of eliciting an undesired anti-murine immunoglobulin immune response, while e.g. the idiotypic immune response and thus the production of endogenous anti-antiidiotypic antibodies should not be affected.